The cis-9,trans-11 isomer of conjugated linoleic acid (CLA) lowers plasma triglyceride and raises HDL cholesterol concentrations but does not suppress aortic atherosclerosis in diabetic apoE-deficient mice

Objective: Reduction in atherosclerosis has been reported in experimental animals fed mixtures of conjugated linoleic acid (CLA). In this study, the major naturally occurring CLA isomer (cis-9,trans-11) was tested in an atherosclerosis-prone mouse model. Methods: In a model of insulin deficient apoE deficient mice, 16 animals were fed for 20 weeks with supplemental CLA (09.%, w/w) and compared with a similar number of mice of this phenotype. A control comparison was made of metabolic changes in non-diabetic apoE deficient mice that develop little atherosclerosis over 20 weeks. At 20 weeks, plasma lipids were measured and aortic atherosclerosis quantified by Sudan staining in the arch, thoracic and abdominal segments. Results: The diabetic apoE deficient mice developed marked dyslipidemia, primarily as cholesterol-enriched chylomicron and VLDL-sized lipoproteins and atherosclerosis in the aortic arch. However, there were no significant differences between CLA fed and non-CLA fed mice in either phenotype in plasma cholesterol concentration (in diabetic: 29.4 +/- 7.7 and 29.5 +/- 5.9 mmol/L, respectively) or in the area of aortic arch atherosclerosis (in diabetic: 24.8 +/- 10.3 and 27.6 +/- 7.7%, respectively). However, among diabetic mice the triglyceride concentration in triglyceride-rich lipoproteins was significantly lower in those fed CLA (for plasma 2.2 +/- 0.8 to 1.1 +/- 0.3 mmol/L; P < 0.001), a significant difference that was seen also in the non-diabetic mice in which HDL cholesterol increased significantly with CLA (0.35 +/- 0.12-0.56 +/- 0.15 mmol/L). Conclusion: In this atherosclerosis-prone model, the diabetic apoE deficient mouse, supplemental 0.9% CLA (cis-9,trans-11) failed to reduce the severity of aortic atherosclerosis, although plasma triglyceride concentration was substantially lowered and HDL cholesterol raised. (c) 2006 Elsevier Ireland Ltd. All rights reserved.